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1.
Early glomerulopathy is present in young,Type 1 (insulin-dependent) diabetic patients with microalbuminuria 总被引:6,自引:0,他引:6
H. -J. Bangstad R. Østerby K. Dahl-Jørgensen K. J. Berg A. Hartmann G. Nyberg S. Frahm Bjørn K. F. Hanssen 《Diabetologia》1993,36(6):523-529
Summary Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli
by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median
age was 19 (range 18–29) years, duration of diabetes 12 (8–15) years, mean blood pressure 93 (87–115) mm Hg, glomerular filtration
rate 132 (101–209) ml·min−1·1.73 m2−2, albumin excretion rate (mean over 1 year) 32 (15–194) μg/min. Reference data were obtained from 11 healthy kidney donors.
Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic
patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix
parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by
light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control
group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549–641 nm) vs 305 nm (287–325 nm),p=0.0001; mesangial volume fraction 0.22 (0.21–0.23) vs 0.19 (0.18–0.21),p=0.04, and matrix volume fraction 0.13 (0.12–0.13 vs 0.09 (0.08–0.10),p=0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly
increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane
thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively. Increment of
basement membrane thickness and matrix volume fraction per year were significantly correlated with mean 1-year HbAlc (r=0.55 andr=0.51, respectively). We conclude that microalbuminuria in Type 1 diabetes is associated with increased basement membrane
thickness and also mesangial matrix expansion. This increment seems to correlate with glycaemic control. 相似文献
2.
Carotid intima-media thickness and stiffness in relation to type 2 diabetes in Chinese 总被引:1,自引:0,他引:1
We investigated carotid intima-media thickness (IMT) and quantitative carotid stiffness (QCS) index in relation to plasma
glycosylated hemoglobin A1C (HbA1C) and duration of diabetes mellitus in 337 Chinese diabetic patients. In categorical analyses, carotid IMT was 710 μm in subjects
with a duration of diabetes mellitus ≤2 years, 760 μm in subjects with a duration of diabetes mellitus more than two years
and with plasma HbA1C < 6.5% (P < 0.05), and 790 μm in subjects with a duration of diabetes mellitus more than two years but with plasma HbA1C ≥ 6.5% (P < 0.01). The corresponding values for QCS values were 4.5, 4.6 and 5.1 (P < 0.05), respectively. In multiple stepwise regression analyses carotid IMT was significantly associated with the duration
of diabetes mellitus, systolic blood pressure and serum concentration of total cholesterol, whereas QCS was significantly
associated with age, HbA1C, systolic and diastolic blood pressure (P < 0.05). In conclusion, carotid IMT as a structural measure of arterial wall is increased in patients with a longer history of diabetes mellitus, whereas
QCS as functional index is mainly influenced by the quality of blood glucose control. 相似文献
3.
Summary Still under debate is the prevalence of microalbuminuria in patients with recently diagnosed Type 2 (non-insulin-dependent)
diabetes mellitus and its relation to existing macro-vascular disease and the major vascular risk markers. Hence, from a representative
sample of 1512 patients with Type 2 diabetes of varied duration (recruited from 22 nonspecialized medical practices of the
Greater Munich Area) 68 (26 males, 42 females) of 71 eligible subjects with a known duration of diabetes of up to 17 weeks
and not less than 4 weeks were examined in the present study. Median age was 61 (39 to 75) years, prevalence of ischaemic
heart disease (case history plus ECG, Minnesota code, Whitehall criteria) 41.2%, and that of peripheral vascular and carotid
artery disease (both assessed by ultrasound-Doppler) were 35.3 and 4.4%, respectively. Diabetes was well controlled (HbA1c: 6.9%, 5.6–8.3; fasting blood glucose: 7.7 mmol/l, 5.4–10.4; median±interquartile range IQ), the cardiovascular risk profile
was most prominent in terms of triglycerides (3.1 mmol/l, 2.1–4.6, median±IQ range) and systolic blood pressure (164 mm Hg,
140–186, median±IQ range). 13.2% showed signs of urinary tract infection. Of the remainder, 19.0% exhibited microalbuminuria
(RIA, >30–200 mg/l), and 5.2% macroalbuminuria (>200 mg/l). Significant correlations (p<0.05) were found between urinary albumin concentration and β2-microglobubin in serum, systolic blood pressure, serum triglycerides, serum HDL-cholesterol (inversely), HbA1c, and peripheral vascular disease. The results suggest a high prevalence of increased urinary albumin excretion in recently
diagnosed Type 2 diabetic patients and a close relationship with several hallmarks of the so-called metabolic syndrome, probably
operative in the pre-clinical state of Type 2 diabetes. Based on these observations, increased albuminuria could be a marker
of early and accelerated atherosclerosis. 相似文献
4.
Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria 总被引:15,自引:0,他引:15
Abstract
Aims/hypothesis. The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent)
diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30–299 mg/g). Methods. Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was
assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE4 years) and by computing the change in urinary albumin excretion during the study (Δ UAE). Results. At baseline, the duration of diabetes averaged 13.3 years (range = 4.0–23.8 years) and the mean glomerular filtration rate
was 159 ml · min–1· 1.73m–2 (range = 98 – 239 ml · min–1· 1.73m–2). Median urinary albumin excretion was 67 mg/g (range = 25–136 mg/g) and it increased to 625 mg/g (range = 9–13471 mg/g)
after 4 years; 10 subjects (63 %; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio ≥ 300 mg/g).
Neither mean arterial pressure nor HbA1 c changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial
cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE4 years, r = –0.49, p = 0.05; ΔUAE, r = –0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression
(UAE4 years, r = 0.11, p = 0.67; ΔUAE, r = 0.09, p = 0.73) and mesangial volume fraction had only a modest effect (UAE4 years,
r = 0.42, p = 0.11; ΔUAE, r = 0.48, p = 0.06). Conclusion/interpretation. Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced
complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important
part in the development and progression of diabetic renal disease. [Diabetologia (1999) 42: 1341–1344]
Received: 29 March 1999 and in final revised form: 16 July 1999 相似文献
5.
Sugawara A Kawai K Motohashi S Saito K Kodama S Yachi Y Hirasawa R Shimano H Yamazaki K Sone H 《Diabetologia》2012,55(8):2128-2131
Aims/hypothesis
The aim of this study was to examine the association between HbA1c variability and the development of microalbuminuria as defined by an albumin/creatinine ratio ≥3.4 mg/mmol (≥30 mg/g) in at least two of three consecutive urine samples in Japanese patients with type 2 diabetes. 相似文献6.
Summary The cumulative incidence of microalbuminuria from onset up to 15 years of Type 1 (insulin-dependent) diabetes mellitus and the relative importance of age, duration, blood pressure and metabolic control for subsequent microalbuminuria was studied in 156 children. Urinary albumin excretion and HbA1c were followed at 3-month intervals from onset and systolic and diastolic blood pressure at the same interval from 5 years of diabetes. Persistent microalbuminuria over 20 g/min developed in 17 children. The cumulative incidence by duration was 24.2% at 15 years of diabetes. Eleven patients developed microalbuminuria after more than 5 years. Among these, first 5-year mean Hb A1c was 8.4 ± 1.3% vs 7.2 ± 1.1% in normoalbuminuric children (p <0.001). The crude relative risk of developing microalbuminuria with a first 5-year mean HbA1c greater than 7.5% was 4.49 (95% confidence interval 1.13–17.84). The age- and duration-adjusted relative risk was 3.51% (0.90–14.42). The year before transition to microalbuminuria neither mean HbA1c nor yearly mean blood pressures, sex or age at onset of diabetes differed from normoalbuminuric children at the same diabetes duration. Age and duration were higher (p = 0.04). The relative importance of early vs later hyperglycaemia, yearly blood pressures, age, age at onset and duration of diabetes for increased albumin excretion rate after more than 5 years, was shown in a multiple regression analysis where the first 5-year mean HbA1c was the only independent predictor (p = 0.02). Six patients had an onset of microalbuminuria before 5 years of diabetes. In this group age, age at onset and yearly mean HbA1c levels did not differ from normoalbuminuric children at the same duration. We conclude that one-fourth of diabetic youth under the age of 21 years develop microalbuminuria within 14 years of diagnosis. Some patients have an early onset of microalbuminuria, not necessarily related to hyperglycaemia, while in later onset cases early hyperglycaemia is strongly related to subsequent microalbuminuria. 相似文献
7.
Low serum magnesium levels and metabolic syndrome 总被引:4,自引:0,他引:4
Low serum magnesium levels are related to diabetes mellitus (DM) and high blood pressure (HBP), but as far as we know, there
are no previous reports that analyzed the serum magnesium concentration in individuals with metabolic syndrome (MS). We performed
a cross-sectional population-based study to compare 192 individuals with MS and 384 disorder-free control subjects, matched
by age and gender. Magnesium supplementation treatment and conditions likely to provoke hypomagnesemia, including previous
diagnosis of diabetes mellitus (DM) and/or high blood pressure (HBP), were exclusion criteria. In this regard, only incident
cases of DM and HBP were included. MS was defined by the presence at least of two of the following features: hyperglycemia
(≥7.0 mmol/l); HBP (≥160/90 mmHg); dyslipidemia (fasting triglycerides ≥1.7 mmol/l and/or HDLcholesterol <1.0 mmol/l); and
obesity (body mass index ≥30 kg/m2 and/or waist-to-hip ratio ≥0.85 in women or ≥0.9 in men). Low serum magnesium levels were identified in 126 (65.6%) and 19
(4.9%) individuals with and without MS, p<0.00001. The mean serum magnesium level among subjects with MS was 1.8±0.3 mg/dl, and among control subjects 2.2±0.2 mg/dl,
p<0.00001. There was a strong independent relationship between low serum magnesium levels and MS (odds ratio (OR)=6.8, CI95% 4.2–10.9). Among the components of MS, dyslipidemia (OR 2.8, CI95% 1.3–2.9) and HBP (OR 1.9, CI95% 1.4–2.8) were strongly related to low serum magnesium levels. This study reveals a strong relationship between decreased
serum magnesium and MS.
Received: 19 July 2001 / Accepted in revised form: May 2002
Correspondence to F. Guerrero-Romero 相似文献
8.
Glomerular hyperfiltration in microalbuminuric NIDDM patients 总被引:3,自引:0,他引:3
P. Vedel J. Obel F. S. Nielsen L. E. Bang T. L. Svendsen O. B. Pedersen H.-H. Parving 《Diabetologia》1996,39(12):1584-1589
Summary Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy
in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarse in microalbuminuric non-insulin-dependent
diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i. v. bolus
injection of 51Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and
20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected
(ml/min) and the adjusted (ml · min–1· 1.73 m–2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 ± 29 and 117 ± 24 as compared
to 115 ± 19 and 99 ± 15; 111 ± 23 and 98 ± 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml · min–1· 1.73 m–2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients
(n = 96): 119 ± 22 as compared to 100 ± 14 and 98 ± 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM
patients) was demonstrated in 37 (95 % confidence interval 30–45)% of the microalbuminuric patients. Multiple regression analysis
revealed that HbA1 c, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric
NIDDM patients (r
2 = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also
characterized by an additional putative risk factor for progression, glomerular hyperfiltration. [Diabetologia (1996) 39:
1584–1589] 相似文献
9.
Summary Abnormal erythrocyte sodium-lithium countertransport (Na-Li CT) activity, traditionally measured at a single sodium concentration
of 140 mmol · l–1 (V140), may represent an inherited risk marker for diabetic nephropathy. The membrane defect underlying this association is poorly
understood, though modulation by key protein thiol groups appears to be important in essential hypertension. To improve understanding
of this abnormality, Na-Li CT kinetics in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide were
investigated in 18 subjects with diabetic nephropathy, 20 normoalbuminuric insulin-dependent diabetic (IDDM) subjects and
18 non-diabetic individuals. Using the traditional assay, V140 was similar in subjects with diabetic nephropathy compared to IDDM control subjects vs 0.311 (0.152–0.475) (0.247 (0.111–0.498)
mmol Li · h–1· l erythrocytes–1). Kinetic parameters were abnormal in subjects with diabetic nephropathy compared with diabetic and non-diabetic control
subjects, with both Vmax (maximal Na-Li CT activity) (0.454 (0.257–0.963) vs 0.338 (0.183–0.972) vs 0.332 (0.213–0.603) mmol Li · h–1· l erythrocytes–1, p < 0.05), and Vmax/Km(So) ratio, reflecting ion association (6.03 (2.3–9.6) vs 4.73 (2.0–10.4) vs 4.48 (1.5–7.1), p < 0.01), significantly higher. N-ethylmaleimide decreased Km(So) and Vmax abolishing differences in Vmax/Km(So) ratio between groups (2.45 (1.18–4.21) vs 2.23 (0.96–4.3) vs 2.44 (1.4–3.7), but enhancing the differences in Vmax (0.186 (0.090–0.315) vs 0.120 (0.051–0.256) vs 0.128 (0.080–0.206) mmol Li · h–1· l erythrocytes–1, p < 0.0001). Of subjects with diabetic nephropathy, 78 % were outside the 75th percentile of the non-diabetic control subjects
when Vmax and Vmax/Km(So) ratio were combined, compared to 20 % of the normoalbuminuric control subjects. We conclude that the traditional assay,
V140, is poor at detecting individuals with diabetic nephropathy. Study of the kinetic parameters of the transporter, including
thiol group modulation, suggests that increased ion association, Vmax/Km(So) ratio may represent the inherited defect and improves identification of subjects with diabetic nephropathy. [Diabetologia
(1997) 40: 1079–1084]
Received: 17 January 1997 and in revised form: 5 May 1997 相似文献
10.
Levitan EB Liu S Stampfer MJ Cook NR Rexrode KM Ridker PM Buring JE Manson JE 《Diabetologia》2008,51(2):267-275
Aims/hypothesis Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk
of death is uncertain. We examined the association between HbA1c measured in stored erythrocytes and mortality rate in women with and without diabetes.
Methods We conducted a cohort study of 27,210 women ≥ 45 years old with no history of cardiovascular disease or cancer who participated
in the Women’s Health Study, a randomised trial of vitamin E and aspirin.
Results Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension,
blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative
risk of mortality. Among women without a diagnosis of diabetes and HbA1c <5.60%, those in the top quintile (HbA1c 5.19–5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98–1.69, p value for linear trend = 0.14) compared with those with HbA1c 2.27–4.79%. Women with HbA1c 5.60–5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1–136%) compared with those with HbA1c 2.27–4.79%. HbA1c was significantly associated with mortality across the range 4.50–7.00% (p value for linear trend = 0.02); a test of deviation from linearity was not statistically significant (p = 0.67). Diabetic women had more than twice the mortality risk of non-diabetic women.
Conclusions/interpretation This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated
with increased risk of mortality.
ClinicalTrials.gov ID no.: NCT00000479 相似文献
11.
Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75) 总被引:13,自引:0,他引:13
Aims/hypothesis The relative importance of glucose and blood pressure control in type 2 diabetes remains uncertain. We assessed interactive effects of glycaemia and systolic blood pressure (SBP) exposure on the risk of diabetic complications over time.Subjects, materials and methods HbA1c and SBP, measured annually for a median of 10.4 years in 4,320 newly diagnosed type 2 diabetic patients from the UK Prospective Diabetes Study (UKPDS), were categorised as updated mean values <6.0, 6.0–6.9, 7.0–7.9 or ≥8.0%, and <130, 130–139, 140–149 or ≥150 mmHg, respectively. Clinical outcomes were UKPDS predefined composite endpoints.Results The incidence of the ‘any diabetes-related endpoint’ in the lowest (HbA1c <6.0%, SBP <130 mmHg) and highest (HbA1c ≥8%, SBP ≥150 mmHg) category combinations was 15 and 82 per 1,000 person-years, respectively, and 24 and 120 per 1,000 person-years in a Poisson model adjusted to white Caucasian male sex, age 50 to 54 years and diabetes duration of 7.5 to 12.5 years. Updated mean HbA1c and SBP effects were additive in an adjusted proportional hazards model with risk reductions of 21% per 1% HbA1c decrement and 11% per 10 mmHg SBP decrement. Endpoint rates obtained in the 887 patients randomised in both the glycaemia and hypertension intervention trial arms were consistent with the observational data. Those allocated to both intensive glucose and tight blood pressure control policies had fewer events than those allocated to either policy alone or to neither (p for trend 0.024).Conclusions/interpretation Risk of complications in type 2 diabetes is associated independently and additively with hyperglycaemia and hypertension. Intensive treatment of both these risk factors is required to minimise the incidence of complications. 相似文献
12.
A. Curtin P. Deegan D. Owens P. Collins A. Johnson G. H. Tomkin 《Acta diabetologica》1995,32(4):244-250
We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with
non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial
lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum
triglyceride levels (serum triglyceride <2.1 mmol l−1; haemoglobin HbA1c 5.5%±0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride >2.1
mmol 1−1; HbA1c 8.8%±0.9%); nondiabetic subjects with serum triglycerides <2.1 mmoll−1; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride>2.1 mmol l−1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was
isolated by ultracentrifugation (d<1.006 g ml−1). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%–15% gradient gels and quantified as a percentage
of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein
B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before
falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic
control subjects whose levels decreased after 2 h (P<0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic
patients (P<0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in
the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated
with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled
diabetic and non-diabetic subjects. 相似文献
13.
Aims/hypothesis: The pathogenesis of fasting hyperglycaemia in Type II (non-insulin-dependent) diabetes mellitus has yet to be clarified.
Rates of glucose production (R
a), utilization and metabolic clearance rate were therefore measured during an extended fast, in control subjects and in Type
II diabetic patients.
Methods: Nine subjects with newly-diagnosed or diet-treated diabetes and seven control subjects matched for age and weight (BMI 36.0
± 2.4 and 35.3 ± 3.1 kg/m2 respectively) underwent an overnight fast followed by a 10-h unprimed infusion of [6-3H]glucose. Plasma tracer concentrations were fitted by a single-compartment model.
Results: The metabolic clearance rate was near-constant [61.7 + 2.4 ml/(min-m2)] in diabetic patients and [75.5 ± 3.3 ml/(min-m2)] in control subjects (p < 0.05). It was correlated to the glucose concentrations both at t = 0 (r = –0.752, p = 0.0008) and t = 10 h (r = –0.675, p = 0.004). The calculated volume of distribution was 17.3 ± 1.4 l (18.2 % weight, diabetes), 19.6 ± 2.4 l (18.4 % weight,
control). Glycaemia fell from 10.7 ± 0.8 mmol/l to 6.5 ± 0.3 mmol/l by 10 h (p < 0.05) in diabetes and from 5.6 ± 0.6 to 4.8 ± 0.1 mmol/l in control subjects (p < 0.05). The rate of glucose production decreased in parallel, from 563 ± 33 to 363 ± 23 μmol/(min-m2) (p < 0.05) in diabetes from 419 ± 20 to 347 ± 32 μmol/(min-m2) in control subjects. Initial R
a was higher in diabetic patients than in control subjects (p < 0.05) and was highly correlated to glycaemia (r = 0.836, p = 0.0001). By 10 h, R
a had converged in diabetic patients and control subjects and all correlation with glycaemia was lost (r = 0.0017, p = 0.95).
Conclusions/interpretation: In relatively early diabetes, the more “labile” portion of fasting hyperglycaemia, which subsequently decreased, was closely
related to the simultaneously decreasing R
a. The 25 % increase in glucose concentrations which persisted as stabilized R
a, resulted from about a 20 % lower metabolic clearance rate. [Diabetologia (2001) 44: 983–991]
Received: 28 February 2001 and in revised form: 17 April 2001 相似文献
14.
Intramuscular triglyceride content is increased in IDDM 总被引:7,自引:0,他引:7
Summary Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular
sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men
(age 29 ± 2 years, BMI 23.3 ± 0.6 kg/m2) and 17 men with insulin-dependent diabetes mellitus (IDDM) (age 30 ± 2 years, BMI 22.8 ± 0.5 kg/m2, diabetes duration 14 ± 2 years, HbA1 c 7.7 ± 0.3 %, insulin dose 48 ± 3 U/day). Insulin sensitivity was measured with a 4 h euglycaemic (5 mmol/l) hyperinsulinaemic
(1.5 mU or 9 pmol · kg–1· min–1) clamp accompanied by indirect calorimetry before and at the end of the insulin infusion. A percutaneous biopsy was performed
from m. vastus lateralis for the determination of mTG. At baseline the IDDM patients had higher glucose (10.2 ± 0.9 vs 5.6
± 0.1 mmol/l, p < 0.001), insulin (40.3 ± 3.2 vs 23.2 ± 4.2 pmol/l, p < 0.01), HDL cholesterol (1.28 ± 0.06 vs 1.04 ± 0.03 mmol/l, p < 0.01) and mTG (32.9 ± 4.6 vs 13.6 ± 2.7 mmol/kg dry weight, p < 0.01) concentrations than the healthy men, respectively. The IDDM patients had lower insulin stimulated whole body total
(–25 %, p < 0.001), oxidative (–18 %, p < 0.01) and non-oxidative glucose disposal rates (–43 %, p < 0.001), whereas lipid oxidation rate was higher in the basal state ( + 44 %, p < 0.01) and during hyperinsulinaemia ( + 283 %, p < 0.05). mTG concentrations did not change significantly during the clamp or correlate with insulin stimulated glucose disposal.
In healthy men mTG correlated positively with lipid oxidation rate at the end of hyperinsulinaemia (r = 0.75, p < 0.05). In conclusion: 1) IDDM is associated with increased intramuscular TG content. 2) mTG content does not correlate
with insulin sensitivity in healthy subjects or patients with IDDM. [Diabetologia (1998) 41: 111–115]
Received: 12 June 1997 and in revised form: 8 September 1997 相似文献
15.
F. Piarulli G. Sartore A. Ceriello E. Ragazzi R. Reitano L. Nollino C. Cosma D. Fedele A. Lapolla 《Diabetologia》2009,52(7):1419-1425
Aims/hypothesis This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria
in patients with type 2 diabetes.
Methods The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were
identified and the following variables evaluated: fasting plasma glucose, HbA1c, malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine,
estimated GFR and lipid profile.
Results Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria
(AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without
microalbuminuria (mean ± SD): fasting plasma glucose 9.41 ± 2.88 vs 8.19 ± 1.93 mmol/l, p < 0.05; HbA1c 7.97 ± 1.51 vs 7.39 ± 1.03%, p < 0.05; MDA 1.18 ± 0.35 vs 1.02 ± 0.29 μmol/l, p < 0.05; pentosidine 98.5 ± 24.6 vs 82.9 ± 20.9 pmol/ml, p < 0.005; and AGE 13.2 ± 4.8 vs 10.6 ± 3.8 μg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were
similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and
both oxidation (HbA1c
r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = −0.55, p < 0.001; TRAP r = −0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin
E, TRAP, HbA1c and MDA, but not pentosidine or AGE.
Conclusions/interpretation Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation
of the antioxidant system in the event of increased glyco-oxidation/glycation. 相似文献
16.
D. Dufayet De La Tour D. Raccah M. F. Jannot T. Coste C. Rougerie P. Vague 《Diabetologia》1998,41(9):1080-1084
Summary Erythrocyte Na/K ATPase activity is decreased in Type I diabetic patients; for Type II diabetic patients, literature data
are controversial. Therefore, we have compared this enzymatic activity in 81 patients with Type I diabetes mellitus, 87 with
Type II diabetes mellitus and 75 control subjects. Mean erythrocyte Na/K ATPase activity was lower in the Type I diabetic
patients (285 ± 8 nmol Pi · mg protein–1· h–1) than in the control subjects (395 ± 9 nmol Pi · mg protein–1· h–1) whereas that of the Type II diabetic patients did not differ from that of control subjects. Sex, age, body mass index, and
HbA1 c levels did not influence erythrocyte Na/K ATPase activity. The 25 Type II diabetic patients treated with insulin, however,
had lower Na/K ATPase activity than the 62 on oral treatment (264 ± 18 vs 364 ± 16 nmol Pi · mg protein–1· h–1, p < 0.001) but similar to that of Type I diabetic patients. Among the Type II diabetic patients, stepwise regression analysis
showed that fasting C-peptide level was the only factor independently correlated with Na/K ATPase activity; it explained 23
% of its variance. In fact, in the insulin-treated patients, those with almost total endogenous insulin deficiency (C-peptide
< 0.2 nmol · l–1) had the lower Na/K ATPase activity (181 ± 21 vs 334 ± 17 nmol Pi · mg protein–1· h–1, p < 0.0001). The biological effects of treatment with C-peptide have recently led to the suggestion that this peptide could
have a physiological role through the same signalling pathway as insulin, involving G-protein and calcium phosphatase and
thus restoring Na/K ATPase activity. The relationship we describe between endogenous C-peptide and this activity is a strong
argument for this physiological role. [Diabetologia (1998) 41: 1080–1084]
Received: 6 November 1997 and in final revised form: 10 April 1998 相似文献
17.
E. L. M. Barr E. J. Boyko P. Z. Zimmet R. Wolfe A. M. Tonkin J. E. Shaw 《Diabetologia》2009,52(3):415-424
Aims/hypothesis Hyperglycaemia is a risk factor for cardiovascular disease (CVD) and all-cause mortality in individuals without diabetes.
We investigated: (1) whether the risk of all-cause and CVD mortality extended continuously throughout the range of fasting
plasma glucose (FPG), 2 h plasma glucose (2hPG) and HbA1c values; and (2) the ability of these measures to improve risk prediction for mortality.
Methods Data on 10,026 people aged ≥25 years without diagnosed diabetes were obtained from the population-based Australian Diabetes,
Obesity and Lifestyle study. Between 1999 and 2000, FPG, 2hPG and HbA1c were assessed and all-cause (332 deaths) and CVD (88 deaths) mortality were obtained after 7 years.
Results Both 2hPG and HbA1c exhibited linear relationships with all-cause and CVD mortality, whereas FPG showed J-shaped relationships. The adjusted
HR (95% CI) for all-cause mortality per SD increase was 1.2 (1.1–1.3) for 2hPG and 1.1 (1.0–1.2) for HbA1c. The HR for FPG <5.1 mmol/l (per SD decrease) was 2.0 (1.3–3.0); for FPG ≥5.1 mmol/l (per SD increase) the HR was 1.1 (1.0–1.2).
Corresponding HRs for CVD mortality were 1.2 (1.0–1.4), 1.2 (1.0–1.3), 4.0 (2.1–7.6) and 1.3 (1.1–1.4). The discriminative
ability of each measure was similar; no measure substantially improved individual risk identification over traditional risk
factors.
Conclusions/interpretation In individuals without diagnosed diabetes, 2hPG and FPG, but not HbA1c were significant predictors of all-cause mortality, whereas all measures were significant predictors of CVD mortality. However,
these glucose measures did not substantially improve individual risk identification. 相似文献
18.
Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone 总被引:12,自引:0,他引:12
Summary Insulin resistance is associated with a decreased vasodilator response to insulin. Because insulin's vasodilator effect is
nitric oxide dependent, this impairment may reflect endothelial dysfunction. Troglitazone, an insulin-sensitiser, might thus
improve insulin-dependent and/or endothelium-dependent vascular function in insulin resistant obese subjects. For 8 weeks,
fifteen obese subjects were treated with either 400 mg troglitazone once daily or placebo, in a randomised, double-blind,
cross-over design. At the end of each treatment period, we measured forearm vasodilator responses (plethysmography) to intra-arterial
administered acetylcholine and sodium nitroprusside; insulin sensitivity and insulin-induced vascular and neurohumoral responses
(clamp); vasoconstrictor responses to N
G-monomethyl-L-arginine (L-NMMA) during hyperinsulinaemia; and ambulatory 24-h blood pressure (ABPM). Baseline data (placebo)
of obese subjects were compared with those obtained in lean control subjects. Obese subjects were insulin resistant compared
with leans (whole-body glucose uptake: 26.8 ± 3.0 vs. 53.9 ± 4.3 μmol · kg–1· min–1, p < 0.001). Troglitazone improved whole-body glucose uptake (to 31.9 ± 3.3 μmol · kg–1· min–1, p = 0.028), and forearm glucose uptake (from 1.09 ± 0.54 to 2.31 ± 0.69 μmol · dL–1· min–1, p = 0.006). Insulin-induced vasodilatation was blunted in obese subjects (percent increase in forearm blood flow (FBF) in lean
66.5 ± 23.0 %, vs. 10.1 ± 11.3 % in obese, p = 0.04), but did not improve during troglitazone. Vascular responses to acetylcholine, sodium nitroprusside and L-NMMA did
not differ between the obese and lean group, nor between both treatment periods in the obese individuals. In conclusion,
in insulin resistant obese subjects, endothelial vascular function is normal despite impaired vasodilator responses to insulin.
Troglitazone improved insulin sensitivity but it had no effects on endothelium-dependent and -independent vascular responses.
These data do not support an association between insulin resistance and endothelial function. [Diabetologia (1998) 41: 569–576]
Received: 19 September 1997 and in revised form: 22 December 1997 相似文献
19.
The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II Diabetic subjects 总被引:6,自引:2,他引:6
Yudkin JS Panahloo A Stehouwer C Emeis JJ Bulmer K Mohamed-Ali V Denver AE 《Diabetologia》2000,43(9):1099-1106
Aims/hypothesis. Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent)
mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial
dysfunction and of acute phase activation, using both sulphonylureas and insulin. Methods. In a randomised cross-over study we gave sulphonylureas or insulin each for a period of 16 weeks to 22 poorly controlled
Type II diabetic subjects who were being treated by diet. There was a 4 week washout period between each treatment. Subjects
were studied at baseline and at the end of each treatment. Results. Treatment with sulphonylureas and insulin resulted in similar improvements in glycaemic control (glycated haemoglobin, baseline:
11.8 [(SD 2.2)%; after sulphonylureas: 8.6 (1.2)%, p < 0.001; after insulin: 8.6 (1.2)%, p < 0.001] and in insulin sensitivity {metabolic clearance rate of glucose, baseline: median 1.75 [interquartile (IQ) range
1.41, 2.27] ml · kg–1· min–1; after sulphonylureas: 2.41 (1.82, 3.01) ml · kg–1· min–1, p = 0.001; after insulin: 2.23 (1.92, 2.75) ml · kg–1· min–1, p = 0.027}. There were no significant changes in concentrations of endothelial markers von Willebrand factor, cellular fibronectin,
thrombomodulin, tissue plasminogen activator, soluble E-selectin or soluble intercellular adhesion molecule-1 or in urinary
albumin excretion rate after either treatment period. Concentrations of C-reactive protein were not significantly influenced
by sulphonylureas but fell after insulin [baseline: median 4.50 (IQ range 1.37, 6.44) μg · ml–1; sulphonylureas: 2.69 (0.88, 9.65) μg · ml–1 (p = 0.53); insulin: 2.07 (1.16, 5.24) μg · ml–1 (p = 0.017)]. There were, however, no significant effects of either treatment on circulating concentrations of fibrinogen (p = 0.28–0.34) or of the proinflammatory cytokines interleukin-6 or tumour necrosis factor-α (p = 0.65–0.79). Conclusion/interpretation. Markers of endothelial dysfunction and concentrations of proinflammatory cytokines in Type II diabetes are not influenced
by improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced
concentrations of the acute phase marker C-reactive protein. [Diabetologia (2000) 43: 1099–1106]
Received: 11 May 2000 and in revised form: 19 June 2000 相似文献
20.
Hayashino Y Fukuhara S Akiba T Akizawa T Asano Y Saito A Bragg-Gresham JL Ramirez SP Port FK Kurokawa K 《Diabetologia》2007,50(6):1170-1177
Aims/hypothesis There are few data on the target level of glycaemic control among patients with diabetes on haemodialysis. We investigated
the impact of glycaemic control on mortality risk among diabetic patients on haemodialysis.
Subjects and methods Data were analysed from the Dialysis Outcomes Practice Pattern Study (DOPPS) for randomly selected patients on haemodialysis
in Japan. The diagnosis of diabetes at baseline and information on clinical events during follow-up were abstracted from the
medical records. A Cox proportional hazards model was used to evaluate the association between presence or absence of diabetes,
glycaemic control (HbA1c quintiles) and mortality risk.
Results Data from 1,569 patients with and 3,342 patients without diabetes on haemodialysis were analysed. Among patients on haemodialysis,
those with diabetes had a higher mortality risk than those without (multivariable hazard ratio 1.37, 95% CI 1.08–1.74). Compared
with those in the bottom quintile of HbA1c level, the multivariable-adjusted hazard ratio for mortality was not increased in the bottom second to fourth quintiles of
HbA1c (HbA1c 5.0–5.5% to 6.2–7.2%), but was significantly increased to 2.36 (95% CI 1.02–5.47) in the fifth quintile (HbA1c ≥ 7.3%). The effect of poor glycaemic control did not statistically correlate with baseline mortality risk (p = 0.27).
Conclusions/interpretation Among dialysis patients, poorer glycaemic control in those with diabetes was associated with higher mortality risk. This suggests
a strong effect of poor glycaemic control above an HbA1c level of about 7.3% on mortality risk, and that this effect does not appear to be influenced by baseline comorbidity status. 相似文献